The Role of Fluconazole in the Treatment of Candida Endocarditis

Abstract

The treatment of Candida infective endocarditis generally involves infected valve removal accompanied by antifungal therapy with amphotericin B or a lipid-based derivative, with or without flucytosine. While often used as chronic suppressive therapy in these patients, the precise role for fluconazole has not been established. We conducted a meta-analysis of 64 literature cases of Candida endocarditis whose management did not include valve replacement but who received fluconazole, alone or concurrently or in sequence with 1 or more other antifungal drugs.Forty-nine (77%) patients were cured (n = 44) or improved (n = 5), 4 relapsed (6%), and 11 failed (10 of whom died) (17%). Among 19 patients for whom fluconazole was administered as the sole antifungal therapy, 11 (58%) were cured or improved. In contrast, among 45 patients who received 1 or more other antifungal agents in addition to fluconazole, 38 (84%) were cured or improved (p = 0.02). Eighteen of 21 (86%) patients with native valve infection were cured or improved compared with 13 of 19 (68%) patients with prosthetic valve endocarditis (p = 0.13). The mean duration of successful fluconazole regimens was 134 days. Twenty of 21 (95%) patients who received fluconazole as chronic suppressive therapy for ≥6 months were cured. Prognosis was independent of Candida species or patient age. Among 23 historical controls managed with fluconazole-containing antifungal therapy plus valvular surgery, survival was 91%.In conclusion, fluconazole-containing, combination antifungal therapy, with or without concomitant valve replacement, and followed by prolonged, perhaps indefinite fluconazole suppression, is effective in patients with Candida endocarditis.

Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications

“…240,241 The well-recognized risk factors associated with fungal IE (eg, IDU and immunocompromised state) have become less prevalent compared with the presence of a cardiovascular device, including central venous catheters, permanent pacemakers and defibrillators, and prosthetic valves. [240][241][242][243][244][245][246] Fungal IE has been recognized as a cause of early PVE, but a case series from a single medical center demonstrated that 43% of these cases had symptom onset >1 years after prosthetic valve placement. 242 In contrast to the expected older age predilection for the development of IE, patients with fungal IE have been younger, which was somewhat unanticipated, considering the low prevalence of IDU among the cohort.…”

“…After completion of this initial therapy, long-term (lifelong) suppressive therapy with an oral azole is reasonable. 243,244,246 Suppressive therapy has been used in 2 populations. First, because of the high relapse rate of fungal IE and the prolonged delay (years in some cases) in relapse, oral azoles have been administered after combined medical and surgical induction therapy.…”

2015 ESC Guidelines for the management of infective endocarditis

“…Dominują zakażenia Candida i Aspergillus spp. Te ostatnie objawiające się jako IZW z ujemnymi posiewami krwi [199,200]. Śmiertelność jest bardzo wysoka (> 50%), a leczenie wymaga skojarzonej terapii przeciwgrzybicznej i chirurgicznej wymiany zastawki Opcjonalnie można dołączyć streptomycynę (15 mg/kg/24 h w 2 dawkach) przez pierwsze kilka tygodni; c Doksycyklina w skojarzeniu z hydroksychlorochiną (z monitorowaniem stężenia hydroksychlorochiny w osoczu) jest istotnie skuteczniejsza niż doksycyklina w monoterapii [194];…”

“…Dawki podawanych leków są takie same jak w przypadku IZW spowodowanego gronkowcami lub eneterokokami (tab. 16 i 18) [196,197] [135,[198][199][200]. Leczenie przeciwgrzybicze w przypadku IZW spowodowanego przez Candida obejmuje liposomalną amfoterycynę B (lub inne preparaty lipidowe) łącznie z (lub bez) flucytozyną lub echinokandyną w dużych dawkach.…”

“…Leczenie przeciwgrzybicze w przypadku IZW spowodowanego przez Candida obejmuje liposomalną amfoterycynę B (lub inne preparaty lipidowe) łącznie z (lub bez) flucytozyną lub echinokandyną w dużych dawkach. Lekiem z wyboru w przypadku IZW wywołanego przez Aspergillus jest worikonazol, a niektórzy eksperci rekomendują dołączenie echinokandyny lub amfoterycyny B [135,198,200,201]. Zaleca się długotrwałe leczenie supresyjne z zastosowaniem doustnych azoli (flukonazol w przypadku Candida oraz worikonazol w przypadku Aspergillus), czasami do końca życia pacjenta [135,198,201].…”